Abstract
Objective
The function and significance of estrogen receptor β (ERβ) in bladder cancer remains a field of hot debate. In this study, we aimed to (a) evaluate ERβ as a novel prognostic marker of recurrence-free survival and (b) digest the underlying mechanism by elucidating the relationship between ERβ expression and cadherin switch.
Methods
We examined the expression levels of ERβ, E-cadherin and N-cadherin in 42 initial non-muscle-invasive urothelial bladder carcinomas via immunohistochemistry. Correlation analysis was performed among ERβ expression, cadherin switch, and recurrence-free survival. Moreover, in vitro studies were performed to validate the identified correlation using two bladder cancer cell lines RT4 and 253 J. Upon stimulation with an ERβ-selective agonist diarylpropionitrile, E-cadherin, N-cadherin expressions; cell migration, and invasion capacity were assessed.
Results
Expression of ERβ protein was seen in 34 bladder cancer cases (80.9%), and 21 (50%) specimens showed non-cadherin switch (positive E-cadherin and negative N-cadherin). ERβ expression and the non-cadherin switch are both accompanied with better recurrence-free survival. Also, the least ERβ expression was observed in specimens that undergo cadherin switch. Moreover, these results were consistent with our observations in bladder cancer RT4 and 253 J cell lines studies. Diarylpropionitrile stimulation resulted in an increase in E-cadherin, a decrease in N-cadherin expressions and abolished cell migration and invasion.
Conclusion
ERβ is a prognostic marker of recurrence-free rate in non-muscle-invasive bladder cancer, potentially through suppressing cadherin switch, and may act as a potential target for bladder cancer therapy.
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Acknowledgments
This study was supported by Shanghai Municipal Natural Science Foundation (Grant No. 10ZR1423800) and Doctoral Innovation Foundation of Shanghai Jiaotong University School of Medicine (Grant No.BXJ201136).
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No conflict of interest relevant to this article was reported.
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Bangmin Han and Di Cui contributed equally to this article.
An erratum to this article is available at http://dx.doi.org/10.1007/s00345-015-1677-2.
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Han, B., Cui, D., Jing, Y. et al. Estrogen receptor β (ERβ) is a novel prognostic marker of recurrence survival in non-muscle-invasive bladder cancer potentially by inhibiting cadherin switch. World J Urol 30, 861–867 (2012). https://doi.org/10.1007/s00345-011-0819-4
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DOI: https://doi.org/10.1007/s00345-011-0819-4